Mucilage of Cordia dichotoma fruits (Boraginaceae) has been used as an expectorant and treatment of lung diseases and gonorrhea. This study isolated and identified C. dichotoma mucilage as a hypolipidemic agent on blood lipid and antioxidant stress status using hyperlipidemic male albino rats. C. dichotoma mucilage was isolated and its physical and chemical characteristics were evaluated. Mucilage was tested at two doses; 0.5 and 1 g/kg (as 0.05 and 0.1 of determined LD50) orally for 10 weeks. Dietary hyperlipidemia model was used to investigate the potential hypolipidemic. Mucilage has a good swelling index (76.35%) and contains galactose, arabinose and glucouronic acid at molar ratio 5.0:3.7:1.0, respectively. In-vivo hypolipidemic experiment, feeding on high-fat diet caused significant increase in serum lipid profile; Total Cholesterol (TC), Triglycerides (TG), Very Low Density Lipoprotein Cholesterol (VLDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) as well as significant decrease on High Density Lipoprotein Cholesterol (HDL-C). Treatment of two doses of mucilage showed promising hypolipidemic activity represented as normalization all obvious abnormalities lipid profile. Antioxidants enzymes activities; Glutathione Reductase (GR), Glutathione-S-transferase (GST), Glutathione Peroxidase (GPx), Catalase (CAT) and Superoxide Dismutase (SOD) were significantly decreased by administration high-fat diet. Meanwhile, mucilage administration significantly improved them. Mucilage treating significantly improved fatty changes shown in hyperlipidemic rat’s liver. Mucilage has a potential effect to prevent hyperlipidemia and oxidative stress with a good safety margin.